1. Field of the Invention
This invention relates to a polymer gel for medical use. More specifically, the present invention relates to a novel polymer gel for medical use having a drug releasing property. The polymer gel of the present invention is useful as the structural component for wound dressings, adhesives for biological tissues, adhesion preventing agents, bone reinforcing materials, and drug releasing base materials.
2. Description of the Related Art
Gauze and/or ointments have been used conventionally for treating wounds such as injury and burn, ulcer, and decubitus. These have effects of absorbing exudate and preventing the penetration of exogenous bacteria and the like. It has been indicated recently that a variety of growth factors (bFGF, TGF.beta., etc.) promoting wound healing are present in the exudate from the wounds [see Howell, J. M., Current and Future Trends in Wound Healing, Emerg. Med. Clin. North Amer., 10, 655-663 (1992), etc.] Therefore, attention has been focused on an occlusive dressing having the effect of promoting wound healing while holding the growth factor on the wound [Eaglstein, W. E., Experience with biosynthetic dressings, J. Am. Acad. Dermatol., 12, 434-440 (1985)].
In addition, polymer gels have been used conventionally in various applications in medical fields. It has been proposed recently a drug delivery system (DDS) or wound dressing containing a pharmaceutical agent in a polymer gel.
In recent years, occlusive wound dressings made of polyurethane film, hydrocolloid, alginate gel, polyvinyl alcohol sponge, or polyvinyl alcohol hydrogel have come to be known.
Occlusive wound dressings made of polyurethane film, hydrocolloid, alginate gel or the like are excellent in terms of the effect of facilitating healing. Once the dressings are infected with bacteria, however, the bacteria rapidly proliferate because the wet environment is a suitable medium for the bacteria, with a risk of triggering severe infection. For the prevention or treatment of the infection with bacteria, antibiotics are administered systemically or locally, but blood circulation is so poor at wounds with bacterial infection that an effective dose of antibiotics cannot be delivered to the wounds by the systemic administration, or side effects may occur by local administration due to the cytotoxicity of locally administered antibiotics and healing is prevented.
As wound dressings with pharmaceutical agents contained therein, proposed are a wound contact pad as a part of a wound treating device, comprising a mixture alginate salt of an insoluble alginate salt and a soluble alginate salt, and containing an antibiotics or a local anesthesia [see Japanese Language Laid-Open Publication (PCT) No. 501067/1992]; and a wound dressing containing hydrogel, as the structural component, in which a peptide promoting healing of wounds is covalently bound at least at the surface and/or containing a disinfectant (see Japanese Language Laid-Open Publication (PCT) No. 500028/1994).
In the wound dressings disclosed in the Japanese Language Laid-Open Publication (PCT) No. 501067/1992, drugs such as antibacterial agents and local anesthesia may be contained in a gel pad, but the drugs are consistently released because the drugs are not immobilized onto the gel, thus possibly inducing side effects.
In the wound dressing disclosed in Japanese Language Laid-Open Publication (PCT) No. 500028/1994, the surface thereof is chemically bound with a peptide for promoting wound healing and the bonding cannot be cleaved. Thus, the effect of the peptide can be exerted only at a site in contact to the wound dressing.
Specific examples of the drug delivery system are a crosslinked hyaluronate gel containing lipid microspheres with pharmaceutical agents encapsulated therein and being cleavable with OH radicals [see Yui, et al., Polymer Pre-prints, Japan, 42(8), 3186-3188 (1993)]; and cellulose powder bound, through an amino acid residue or peptide chain composed of -Phe-, -Tyr-, -Ile-Tyr- or -Gly-Ile-Tyr-, with pholcodine [see F. Lapicque & E. Dellacherie, J. Controlled Release, 4, 39-45 (1986)].
In the former case, the hyaluronate gel is decomposed at a site where OH radicals are generated, whereby a drug encapsulated in lipid microspheres is released. Because the generation of high levels of OH radicals is limited to a certain stage of inflammation or to a very limited area of inflammation, however, the number of diseases to which the system is applicable is relatively limited. Furthermore, the drug encapsulated into lipid microspheres is gradually released from the lipid microspheres into an external aqueous phase so that the drug may be released also at a site besides the diseased site, involving possible side effects.
In the latter case, pholcodine bound through an amino acid residue or peptide chain composed of -Phe-, -Tyr-, -Ile-Tyr- or -Gly-Ile-Tyr- to cellulose powder is tentatively released by the cleaving action of an enzyme, but the release of the drug is as less as 1/1000 to 1/20,000 fold compared with the unimmobilized drug. Thus, such system is not practical.